Cross-reactive CD8+ T cell responses to tumor-associated antigens (TAAs) and homologous microbiota-derived antigens (MoAs)
© 2024. The Author(s)..
BACKGROUND: We have recently shown extensive sequence and conformational homology between tumor-associated antigens (TAAs) and antigens derived from microorganisms (MoAs). The present study aimed to assess the breadth of T-cell recognition specific to MoAs and the corresponding TAAs in healthy subjects (HS) and patients with cancer (CP).
METHOD: A library of > 100 peptide-MHC (pMHC) combinations was used to generate DNA-barcode labelled multimers. Homologous peptides were selected from the Cancer Antigenic Peptide Database, as well as Bacteroidetes/Firmicutes-derived peptides. They were incubated with CD8 + T cells from the peripheral blood of HLA-A*02:01 healthy individuals (n = 10) and cancer patients (n = 16). T cell recognition was identified using tetramer-staining analysis. Cytotoxicity assay was performed using as target cells TAP-deficient T2 cells loaded with MoA or the paired TuA.
RESULTS: A total of 66 unique pMHC recognized by CD8+ T cells across all groups were identified. Of these, 21 epitopes from microbiota were identified as novel immunological targets. Reactivity against selected TAAs was observed for both HS and CP. pMHC tetramer staining confirmed CD8+ T cell populations cross-reacting with CTA SSX2 and paired microbiota epitopes. Moreover, PBMCs activated with the MoA where shown to release IFNγ as well as to exert cytotoxic activity against cells presenting the paired TuA.
CONCLUSIONS: Several predicted microbiota-derived MoAs are recognized by T cells in HS and CP. Reactivity against TAAs was observed also in HS, primed by the homologous bacterial antigens. CD8+ T cells cross-reacting with MAGE-A1 and paired microbiota epitopes were identified in three subjects. Therefore, the microbiota can elicit an extensive repertoire of natural memory T cells to TAAs, possibly able to control tumor growth ("natural anti-cancer vaccination"). In addition, non-self MoAs can be included in preventive/therapeutic off-the-shelf cancer vaccines with more potent anti-tumor efficacy than those based on TAAs.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
|---|---|
| Enthalten in: |
Journal of experimental & clinical cancer research : CR - 43(2024), 1 vom: 20. März, Seite 87 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Cavalluzzo, Beatrice [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Antigens, Neoplasm |
|---|
| Anmerkungen: |
Date Completed 22.03.2024 Date Revised 23.03.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1186/s13046-024-03004-z |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369991524 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369991524 | ||
| 003 | DE-627 | ||
| 005 | 20240323235555.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240322s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s13046-024-03004-z |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1342.xml |
| 035 | |a (DE-627)NLM369991524 | ||
| 035 | |a (NLM)38509571 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Cavalluzzo, Beatrice |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cross-reactive CD8+ T cell responses to tumor-associated antigens (TAAs) and homologous microbiota-derived antigens (MoAs) |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 22.03.2024 | ||
| 500 | |a Date Revised 23.03.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a BACKGROUND: We have recently shown extensive sequence and conformational homology between tumor-associated antigens (TAAs) and antigens derived from microorganisms (MoAs). The present study aimed to assess the breadth of T-cell recognition specific to MoAs and the corresponding TAAs in healthy subjects (HS) and patients with cancer (CP) | ||
| 520 | |a METHOD: A library of > 100 peptide-MHC (pMHC) combinations was used to generate DNA-barcode labelled multimers. Homologous peptides were selected from the Cancer Antigenic Peptide Database, as well as Bacteroidetes/Firmicutes-derived peptides. They were incubated with CD8 + T cells from the peripheral blood of HLA-A*02:01 healthy individuals (n = 10) and cancer patients (n = 16). T cell recognition was identified using tetramer-staining analysis. Cytotoxicity assay was performed using as target cells TAP-deficient T2 cells loaded with MoA or the paired TuA | ||
| 520 | |a RESULTS: A total of 66 unique pMHC recognized by CD8+ T cells across all groups were identified. Of these, 21 epitopes from microbiota were identified as novel immunological targets. Reactivity against selected TAAs was observed for both HS and CP. pMHC tetramer staining confirmed CD8+ T cell populations cross-reacting with CTA SSX2 and paired microbiota epitopes. Moreover, PBMCs activated with the MoA where shown to release IFNγ as well as to exert cytotoxic activity against cells presenting the paired TuA | ||
| 520 | |a CONCLUSIONS: Several predicted microbiota-derived MoAs are recognized by T cells in HS and CP. Reactivity against TAAs was observed also in HS, primed by the homologous bacterial antigens. CD8+ T cells cross-reacting with MAGE-A1 and paired microbiota epitopes were identified in three subjects. Therefore, the microbiota can elicit an extensive repertoire of natural memory T cells to TAAs, possibly able to control tumor growth ("natural anti-cancer vaccination"). In addition, non-self MoAs can be included in preventive/therapeutic off-the-shelf cancer vaccines with more potent anti-tumor efficacy than those based on TAAs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Epitopes, T-Lymphocyte |2 NLM | |
| 650 | 7 | |a Antigens, Neoplasm |2 NLM | |
| 650 | 7 | |a Peptides |2 NLM | |
| 700 | 1 | |a Viuff, Marie Christine |e verfasserin |4 aut | |
| 700 | 1 | |a Tvingsholm, Siri Amanda |e verfasserin |4 aut | |
| 700 | 1 | |a Ragone, Concetta |e verfasserin |4 aut | |
| 700 | 1 | |a Manolio, Carmen |e verfasserin |4 aut | |
| 700 | 1 | |a Mauriello, Angela |e verfasserin |4 aut | |
| 700 | 1 | |a Buonaguro, Franco M |e verfasserin |4 aut | |
| 700 | 1 | |a Tornesello, Maria Lina |e verfasserin |4 aut | |
| 700 | 1 | |a Izzo, Francesco |e verfasserin |4 aut | |
| 700 | 1 | |a Morabito, Alessandro |e verfasserin |4 aut | |
| 700 | 1 | |a Hadrup, Sine Reker |e verfasserin |4 aut | |
| 700 | 1 | |a Tagliamonte, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Buonaguro, Luigi |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of experimental & clinical cancer research : CR |d 1994 |g 43(2024), 1 vom: 20. März, Seite 87 |w (DE-627)NLM08283427X |x 1756-9966 |7 nnns |
| 773 | 1 | 8 | |g volume:43 |g year:2024 |g number:1 |g day:20 |g month:03 |g pages:87 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1186/s13046-024-03004-z |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 43 |j 2024 |e 1 |b 20 |c 03 |h 87 | ||